Tailoring Stress Cardiac MRI for Women with Ischemic Heart Disease

项目摘要 慢性缺血性心脏病(IHD)是一个耗资104亿美元的问题，占死亡人数的45.1% 可归因于心血管疾病。与男性相比，女性患IHD的谱系不同。当前 诊断工具遵循一刀切的模式，旨在检测IHD的男性模式。诸如以下问题 由于乳房组织、肥胖和肺部疾病使超声或核技术等工具变得容易获得 SPECT成像对女性的限制更大。无梗阻性冠状动脉病变的缺血性更常见 女性与男性相比；有症状的女性比无症状的女性面临更高的主要心脏事件发生率 女人。因此，准确的非侵入性工具能够表征整个IHD频谱和 其相关的缺血负荷对有缺血症状的女性的临床治疗具有重要意义。侵入性 干预措施没有风险，缺乏治疗方法会导致残疾。发生心肌缺血 当代谢需求和血液供应不平衡时。尽管组织血液供应 同时受心肌血流量(MBF)和心肌血容量(MBV)的影响， 这些策略侧重于测量MBF的缺陷，而MBF本身可能并不能反映心肌缺血的所有方面。 为了更好地反映缺血负荷，我们提出了一种基于MBV的、全心、无Gd、非... 肾毒性，阿魏酸甘油酯增强，心脏磁共振成像(MRI)负荷测试 将检测到可诱发的缺血的方法。我们基于我们在阿魏酸甘油酯增强磁共振成像方面的经验 通过在缺血的临床前模型中测试我们的策略来增加严谨性；我们有效地将我们的方法转化为 通过在患有IHD的妇女身上验证这项技术的临床应用，其中一些妇女需要阿魏酸甘油来治疗 目的。由于全球有20亿人缺铁，阿魏酸甘油酯的双重使用可作为一种诊断 压力测试中的治疗剂代表了一种量身定做压力心脏MRI的方法 对于经常缺铁的女性来说。我们项目的成功完成将会产生一种-- 免费、阿魏酸甲酯增强的MRI负荷测试方法，可以可靠地区分正常和 并将为发展心肌负荷测试奠定基础 能够同时询问心外膜和微血管的IHD的方法。

PROJECT ABSTRACT Chronic ischemic heart disease (IHD) is a $10.4-billion-dollar problem that is responsible for 45.1% of deaths attributable to cardiovascular disease. Compared to men, women have a different spectrum of IHD. Current diagnostic tools follow a one-size-fits-all model and are designed to detect a male pattern of IHD. Issues such as breast tissue, obesity, and lung disease render easily accessible tools such as ultrasound or nuclear SPECT imaging more limiting for women. Ischemia with no obstructive coronary disease is more common in women compared to men; symptomatic women face higher rates of major cardiac events than asymptomatic women. Therefore, accurate non-invasive tools that enable characterization of the entire spectrum of IHD and its correlative ischemic burden are crucial for clinical management of women with ischemic symptoms. Invasive interventions are without risks and lack of therapeutics contributes to disability. Myocardial ischemia occurs when there is an imbalance between metabolic demand and blood supply. Although tissue blood supply is affected by both myocardial blood flow (MBF) and myocardial blood volume (MBV), current stress perfusion strategies focus on measuring deficits in MBF, which alone may not reflect all aspects of myocardial ischemia. To better reflect the ischemic burden, we propose an MBV-based, whole-heart, gadolinium-free, non- nephrotoxic, ferumoxytol contrast-enhanced, cardiac magnetic resonance imaging (MRI) stress testing approach that will detect inducible ischemia. We build upon our experience in ferumoxytol-enhanced MRI and add rigor by testing our strategy in pre-clinical models of ischemia; we efficiently translate our approach to the clinic by validating the technique in women with IHD, some of whom require ferumoxytol for therapeutic purposes. Because 2 billion people worldwide have iron deficiency, the dual use of ferumoxytol as a diagnostic and therapeutic agent in the context of stress testing represents one approach to tailoring stress cardiac MRI for women who are frequently iron deficient. Successful completion of our project would result in a gadolinium- free, ferumoxytol-enhanced MRI stress testing approach that can reliably differentiate between normal vs ischemic myocardial tissue and would establish a foundation for development of myocardial stress testing approaches that enable interrogation of both epicardial and microvascular IHD.